Meliazedins A-H, limonoids with cytotoxicity and inhibitory activity on lysosomal acidification from Melia azedarach L.

Eight undescribed limonoids named meliazedins A-H (1-8), along with nineteen known limonoids (9-27), were isolated from the bark of Melia azedarach L. The structures of the undescribed ones were elucidated by 1D/2D NMR spectroscopy, mass spectrometry and ECD calculations. Meliazedins A-H were evaluated for their cytotoxicity against three human tumor cell lines (K562, MDA-MB-231, and SW480) and all isolates were evaluated for their activities on lysosomal acidification. Compounds 3, 5, 7 exhibited IC50 values of 0.035-5.583 μM against three tumor cell lines. 21 compounds showed a decrease in red fluorescence intensity in cells with LysoTracker Red staining. Further investigation revealed that meliazedin C (3) was able to induce lysosomal dysfunction via the inhibition of lysosomal acidification suggested that this limonoid has potential on lysosomal-related diseases.